Herrlinger, K. R. and Fellermann, K. and Fischer, C. and Kreisel, W. and Deibert, P. and Schoelmerich, Juergen and Fleig, W. E. and Ruhl, A. and Reinshagen, M. and Greinwald, R. and Stange, E. F. and Schwab, M. (2004) Thioguanine-nucleo tides do not predict efficacy of tioguanine in Crohn's disease. ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 19 (12). pp. 1269-1276. ISSN 0269-2813, 1365-2036
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Background: 6-Thioguanine-nucleotides seem to be the active metabolites of thiopurine therapy, and their monitoring has been considered a useful tool for optimizing response in inflammatory bowel diseases. Tioguanine (thioguanine) therapy results in much higher levels of 6-thioguanine-nucleotide levels when compared with azathioprine or mercaptopurine. Aim: To elucidate the influence of 6-thioguanine-nucleotide and methylated 6-thioguanine-nucleotide levels under tioguanine on efficacy and toxicity in Crohn's disease. Methods: 6-Thioguanine-nucleotide and methylated 6-tioguanine-nucleotide levels were measured regularly in 26 Crohn's disease patients treated with tioguanine. Nucleotide levels were related to efficacy and toxicity. Results: 6-Thioguanine-nucleotide levels rose very high [median 1241 pmol/8 x 10(8) red blood cells (range 313-1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 X 108 red blood cells (154-1775)]. 6-Thioguanine-nucleotide and methylated 6-thioguanine-nucleotide concentrations correlated significantly (r = 0.7, P < 0.0001). Nucleotide levels from patients achieving remission (n = 14) did not differ significantly from non-remitters (n = 12) [6-thioguanine-nucleotide: 1077 (599-2160) vs. 1210 (534-4665); methylated 6-thioguanine-nucleotide: 510 (214-1222) vs. 421 (145-1284)]. One patient with intermediate thiopurine S-methyltransferase activity experienced bone marrow toxicity upon dose escalation parallel with excessively high thioguanine-nucleotide levels. Conclusions: 6-Thioguanine-nucleotide as well as methylated 6-thioguanine-nucleotide levels under tioguanine therapy were not related to efficacy. This suggests that monitoring of 6-thioguanine-nucleotide levels is not a useful tool to predict response to thiopurines.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THIOPURINE S-METHYLTRANSFERASE; INFLAMMATORY-BOWEL-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; AZATHIOPRINE THERAPY; 6-MERCAPTOPURINE THERAPY; 6-THIOGUANINE; METABOLITE; MERCAPTOPURINE; CHILDREN; PHARMACOGENOMICS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jul 2021 12:44 |
| Last Modified: | 12 Jul 2021 12:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37535 |
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